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Brain protein holds the key for understanding drug addiction

A new explanation for how the brain becomes wired towards drug addiction at the expense of other rewards has been put forward by University of Sussex researchers.

Drug addiction comes about because drugs take over processes in the brain that normally help us to respond to natural motivators like food and sex.

For many years scientists have known that the accumbens area of the brain plays a decisive role in seeking both natural and drug-related 'highs'. The nerve cells in this area talk to one another using the chemical messenger GABA. Now a report in the Proceedings of the National Academy of Sciences of the USA shows that one of the receptor proteins for GABA plays a special role in helping the accumbens decide how to prioritise motivations, whether to go for chips or salad, or perhaps even for cocaine.

Experimental psychologists Professor Dai Stephens, Dr Claire Dixon and their colleagues at the University of Sussex found changes in behaviour that occur during persistent drug taking, and which contribute to addiction, is linked to a particular GABA receptor protein (alpha2). If this receptor protein is genetically removed, willingness to work for natural rewards such as food, and even for a single dose of cocaine is normal. However, behavioural changes that come about with repeated cocaine use, and which bias reward-seeking towards drugs at the expense of other rewards, do not develop.

Professor Stephens explains: "In everyday life, trivial occurrences that happen at the same time as pleasant events become rewarding in their own right, just like the bell used with Pavlov's dog that was paired with food and eventually triggered salivation even when food wasn't present. Some heroin addicts (so-called "needle freaks") will stick needles into a vein to get a high, even if the syringe has no heroin in it. These kinds of "conditioned rewards" are increased by drugs like cocaine, so that drugs actually increase the willingness of the addict to work for drug-associated cues."

The University of Sussex researchers found if the gene was removed cues associated with pleasurable events still became rewarding but cocaine did not increase the liking of these cues. With this thought in mind, the Sussex researchers sought help from colleagues at the Institute of Psychiatry in London, and in Sao Paulo, Brazil, to analyse the genetic make up of cocaine addicts and healthy non-drug taking individuals. They found that the addicts were more likely to have an altered form of exactly the same gene that the Sussex team had identified in their laboratory experiments.

The team is now working to understand better the exact part played by the missing gene in cross-talk between accumbens nerve cells. "Eventually, drugs able to inactivate these proteins may be able to help prevent relapse in recovering addicts, but that is some years away," says Prof Stephens.